Congenital heart disease affects 1% of US births, with many babies requiring major cardiothoracic surgery under cardiopulmonary bypass (CPB), exposing the more critical patients to neurodevelopmental impairment. Optimal surgical parameters to minimize neuronal injury are unknown. We used 1H MRS and blood ammonia assays in a neonatal pig model of CPB to compare two approaches, complete circulatory arrest (CA) versus antegrade cerebral perfusion (ACP). Two-week old piglets (N=17) were put on a CPB pump and placed in a 3T MRI to study brain metabolism during CPB. Dynamic single-voxel 1H MRS brain data were acquired while animals underwent one of four CPB protocols: ∼50 min CA at 18ºC and 28ºC or ACP at 18ºC and 28ºC, followed by a ∼1-hr recovery period. Based on 1H MRS findings suggesting the presence of brain ammonia upon reperfusion, a second cohort of piglets (N=22) underwent the same CPB conditions without MRS to allow regular venous blood sampling with ammonia assays. All animals showed a transitory temperature-dependent rise in blood ammonia (p < .001) immediately following restart of whole-body perfusion . In contrast, metabolic processing of brain ammonia, as detected by an increased 1H MRS glutamine/glutamate ratio, was also temperature dependent (p =.002) but only significantly observed in the CA studies (p =.009). Serial 1H-MRS and blood ammonia assays in this preclinical CPB model identified a previously unreported build-up of ammonia, hypothesized to arise from gut bacterial production, following reperfusion, that may contribute to brain injury in these pediatric surgeries.
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